The major cell surface glycoprotein fibronectin is decreased after malignant transformation of fibroblasts and is involved in cellular adhesion. Its role in embryonic differentiation has been examined. Muscle and cartilage cell development appears to require specific alterations in quantities of fibronectin. Fibronectins isolated from the cell surface and from plasma are similar but not identical in either biological activities or polypeptide structure. The collagen binding site of cellular fibronectin was identified and isolated, and a homologous but not identical site is also present on plasma fibronectin. The carbohydrate moiety of fibronectin is not required for a variety of biological activities, but helps to stabilize the protein against proteases and abnormal protein turnover. Other roles of asparagine-linked oligosaccharides were identified in membrane transport and in sulfated proteoglycan synthesis, but not in several membrane enzymatic activities or in protein secretion. Our objectives will be to determine the composition and structure of various active sites on fibronectin, and the mechanisms by which this major cell surface protein helps to regulate cell behavior and differentiation.